There are several hypotheses put forward as to the reduced efficacy of trastuzumab in Fo2-1282 brain lesions compared with mammary tumors: the inability of immune effector cells to access the brain lesion, thereby impairing ADCC; the presence of ErbB ligands in the brain microenvironment circumventing HER2 inhibition by trastuzumab; or activation of compensatory signaling pathways. The gene discussed is EGFR; the disease is breast cancer.